Project Summary/Abstract: Cancer Genes and Molecular Regulation Program (CGMRP) The overall goal of the Cancer Genes and Molecular Regulation Program (CGMRP) is to develop strategies for the identification and validation of cellular targets for cancer therapy, and for the discovery of small molecules and delivery methods that affect target function. The CGMRP has 28 members from nine departments with multidisciplinary interests in cancer target discovery and development. Nine new members have been recruited to the CGMRP over the previous period of funding. The program membership has technical strengths in super- resolution microscopy, high throughput RNA interference, small molecule screening and delivery, synthetic and medicinal chemistry, and the development of evaluative preclinical models. The research interests of the program faculty are organized around three themes: cancer target identification, cancer target validation, and drug delivery/translational development. Investigators within the cancer target identification theme are focused on developing conceptually and technically novel approaches that can be used for the discovery of cancer targets. Investigators within the cancer target validation theme analyze putative targets for cancer therapy and develop and evaluate small molecules directed at those targets. Investigators focused on drug delivery and translational research within the CGMRP analyze and test novel models for cancer therapy and methods for drug delivery. The Co-Directors leverage their expertise to enhance inter- and intra-programmatic collaboration through the development of new shared resources, the evaluation and funding of pilot projects supporting the CGMRP mission, the attraction of high profile speakers for Cancer Center Grand Rounds and regular seminar series, and the organization of monthly programmatic meetings. These activities have promoted a strongly collaborative group as demonstrated by inter- and intra-programmatic publications and grants, and the generation of new clinical trials based on discoveries from CGMRP investigators. 637 cancer-related manuscripts were published by CGMRP investigators during the previous funding period, of which 25% were intra-programmatic, 20% were inter-programmatic publications, and 6% are both intra- and inter-programmatic. The CGMRP has $6.66M in total peer-reviewed funding ($4.67M direct) of which 50% is from the National Cancer Institute.